PHARMACOLOGICAL AND TOXICOLOGICAL STUDIES OF THE METHANOL EXTRACT OF ACACIA ATAXACANTHA LEAF D.C. (LEGUMINOSAE) IN MICE AND RATS
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ABSTRACT
Acacia ataxacantha is used in traditional medicine for management of pain and inflammation. Literature survey revealed that the safety and efficacy of such uses have not been scientifically validated. The present study was designed to study the pharmacological and toxicological activities of methanol extract of Acacia ataxacantha leaf in mice and rats. The acute and chronic toxicity studies were carried out using Lorke method (1983) and OECD guideline (1995) respectively. The extract was evaluated for analgesic activity using acetic acid, formalin and hot plate induced pain assays. Similarly, anti-inflammatory activity was evaluated using carragenaan and albumin induced inflammation, and antipyretic activity using yeast induced pyrexia. Phytochemical screening revealed the presence of flavonoids, alkaloids, glycosides, phenols, tannins and carbohydrate. The oral median lethal dose (LD50) of the extract in both mice and rats was estimated to be > 5000 mg/kg, while the intraperitoneal LD50 in mice and rats were estimated to be 565.69 and 1,264.91 mg/kg respectively. There were significant increase in the level of liver AST, ALT and ALP of the animals after 90 days daily administration of the extract, suggesting that the extract could be hepatotoxic. Similarly, there was significant increase in the levels of urea and creatinine which may indicate toxic effect of the extract on the kidney. The histopathological evaluation revealed adverse effects on the morphology of some organs; liver (mild hepatocellular necrosis and kupfer cell hyperplasia), kidney (glomeruli necrosis and lymphocytes hyperplasia) and stomach (mild necrosis of the stomach mucosa). The extract at doses of 50, 100, 200 and 400 mg/kg significantly (p< 0.05) reduced the number of writhing induced by acetic acid when compared with the negative control. In the thermal pain induction at the 1st hour post extract administration, there was significant (p < 0.05) increase in pain threshold at 400 mg/kg only while, at the 2nd and 3rd hour there were significant differences (p< 0.05) at doses of 50, 100, 200 and 400 mg/kg when compared xvii with the negative control. There was significant (p < 0.05) reduction in pain perception at doses of 50, 100, 200 and 400 mg/kg (first phase) and at 200 and 400 mg/kg (second phase) of formalin pain induction. The carragenaan induced inflammation produced significant (p < 0.05) reduction of inflammation at 200 and 400 mg/kg (2nd hour) while the significant reduction in oedema was observed, in the 3rd and 4th hour, at doses of 100, 200 and 400mg/kg when compared with the negative control. Similarly there was significant inhibition of inflammation at the 20th, 40th 60th and 120th minutes post extract administration in albumin induced inflammation. These findings suggest that the extract may contain bioactive compounds that possess analgesic and anti-inflammatory activities, thus supporting the ethno-medical use of the plant for the management of pain and inflammation. However, prolong use of the extract may produce some adverse effects on the liver, kidney and stomach mucosa.
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